Area:
Systems Neuroscience, Striatum, Behavior, Glutamate
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High-probability grants
According to our matching algorithm, Brenda L. McKee is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2004 — 2005 |
Mckee, Brenda L |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Effects of Cocaine On the Dorsolateral Striatum @ Oregon Health and Science University
DESCRIPTION (provided by applicant): The dorsolateral striatum is involved in mediating habit learning. This habit learning is involved in ritualizatlon of behaviors related to compulsive drug use. It has been reported that acute cocaine administration results in increased expression of the immediate early gene, c-Fos. Furthermore, this cocaine-induced expression can be blocked by prior administration of glutamate receptor antagonists. However, the long-term effects on glutamate in the dorsolateral striatum after acute cocaine administration is not known. The primary goal of this proposal is to investigate the neurochemical and neuroanatomicai changes within the dorsolateral striatum that occur as a result of acute cocaine administration. In vivo microdialysis will be used to determine the striatal changes in extracellular glutamate after an acute cocaine injection. Immunogold electron microscopy will be used to correlate changes in extracellular glutamate with alterations in the density of presynaptic nerve terminal glutamate immunolabeling. To investigate whether cocaine is having an indirect effect on striatal glutamate via the thalamocorticostdatal pathway, the motor thalamic nucleus will be lesioned prior to acute cocaine exposure. Knowledge of the short and long term effects of a single cocaine exposure could promote a better understanding of cocaine use by humans.
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0.94 |
2007 — 2010 |
Mckee, Brenda L |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Homer Upregulation During Instrumental Learning in the Dorsomedial Striatum @ University of Wisconsin Madison
[unreadable] DESCRIPTION (provided by applicant): The basic tenet of operant learning is tested in a laboratory by training rats to press a lever for a reward. When a rat learns to lever press for a sucrose reward, synaptic plasticity immediately occurs in the corticolimbic circuit. An example of this plasticity is the up regulation of an immediate early gene called Homerla. Recent work from Dr. Ann Kelley's laboratory has shown that Homerla has increased expression during the early learning, or acquisition, of operant learning in the dorsomedial striatum and the anterior cingulate cortex (Hernandez et al., 2006). What remains unknown is which cells in the dorsomedial striatum have upregulated Homerla expression, and what are the efferent and afferent projections of these cells. In addition, the anterior cingulate cortex sends a glutamatergic projection to the dorsomedial striatum. To date, the role of this corticostriatal projection and the postsynaptic glutamate receptors in operant learning has not been investigated. It is hypothesized that the .anterior cingulate cortical projection to the dorsomedial striatum mediates operant responding for a sucrose reward, and Homerla is upregulated in the corticostriatal cells that express enkephalin, a neuropeptide linked to food intake. To investigate these hypotheses, glutamate receptor antagonists will be microinjected into the dorsomedial striatum and anterior cingulate cortex to show the role of these areas in operant responding. In addition, tract tracing studies will be combined with in situ hybridization to determine the circuit connectivity of Homerla-expressing cells that are activated during operant responding for a sucrose reward. The knowledge gained from the aims of this proposal is important for furthering the understanding of the molecular changes that occur in different areas of the brain during initial learning. This initial learning that relates to procuring a reward is part of the early learning that initiates during addiction. Addiction is a disease that causes more than 550,000 deaths a year in the United States alone and has an estimated yearly economic cost of $432 billion. Understanding the neural substrates of addiction will help to produce treatments for this devastating disease. [unreadable] [unreadable] [unreadable]
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